The principal purpose of this application is the purchase of a hybrid quadrupole-orthogonal time-of-flight mass spectrometer (Q-tof). An increasing part of th research effort conducted by UAB investigators is identification of the biochemically or chemically modified forms of proteins mediating specific cellular functions (signalling, cell shape, cell motility, etc.) in individual cell lines and in diseased tissues. The increased sensitivity of the Q-tof will allow endogenous, post- translational modifications of proteins to be examined. Chemical modifications may be deliberate (probes to investigate structural or mechanistic hypotheses) or consequential (in the action of a therapeutic drug, one of its metabolites, or other xenobiotics). These will include hydrogen-deuterium exchange experiments which enable the study of protein folding and protein-protein interactions. In many cases, the amounts of the proteins and/or their proteolytic peptides available for analysis is strictly limited (mid-femtomole range), 10-100 times less than can be detected by the existing mass spectrometers in the Mass Spectrometry Shared Facility, or by any chemical sequencing method. The Q-tof instrument, by combining quadrupole ion selection with ion fragmentation and a time-of-flight analyzer, provides the necessary increase in sensitivity to attack these problems. In related applications, investigators will take advantage of the wider m/z range (0-8,000) of the Q-tof to study lower charge states of molecular ions of proteins. This may be a consequence of (1) the amino acid composition of a particular protein, 92) carrying out electrospray experiments at neural pH, or (3) during the study of protein-protein and protein-DNA binding. In summary, the Micromass Q-tof mass spectrometer will substantially enhance the capability of a wide range of UAB faculty carrying our NIH-funded biomedical research.